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LeukemiaPhase 2NCT01682226

Cord Blood With T-Cell Depleted Haplo-identical Peripheral Blood Stem Cell Transplantation for Hematological Malignancies

A Phase 2 study testing CliniMACS Fractionation system (Arm A), CliniMACS Fractionation system (Arm B) and Haploidentical donor CD34+ cells in people with Leukemia and Myelodysplastic Syndrome, run by Memorial Sloan Kettering Cancer Center at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

The purpose of this study is to find out whether the addition of blood stem cells from a close family member, when added to umbilical cord blood will make the transplant safer. Read more about this study

Who is it for?
Ages 2 to 70 yearsHealthy volunteers can take part
Conditions the study is for
Leukemia, Myelodysplastic Syndrome, Lymphoma
What is being tested?
CliniMACS Fractionation system (Arm A), CliniMACS Fractionation system (Arm B) and Haploidentical donor CD34+ cells
Could I receive a placebo?
No, everyone receives an active treatment
How many people
84 participants
Where
1 siteUnited States
Study dates
5 Sep 2012to 8 Jan 2021
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 2 to 70 years
  • All sexes
  • Healthy volunteers accepted
  • Child, Adult, Older adult

Who may be able to join

  • Note: protocol eligible patients according to the criteria outlined below will then be divided according to age, diagnosis, performance status, organ function, prior transplantation, hematopoietic cell transplant comorbidity index (HCT-CI)23, and CB TNC dose into those who are at standard risk (Arm A) or high risk (Arm B) for early post-transplant death for the purposes of applying stopping rules and outcome analysis.
  • Age:
  • o 2 - 70 years. Diagnosis of severe aplastic anemia: eligibility to be discussed with PI and Service Chief. Such patients will be assessed in Arm B.
  • Diagnosis of high risk hematological malignancy:
  • Any acute leukemia in first complete remission (CR) considered at high risk for relapse, or second or third CR, or relapse/refractory less than 10% blasts in bone marrow, or aplasia post-therapy. This includes de novo acute leukemia or acute leukemia that is therapy related or arising from an antecedent hematologic disorder including myelodysplasia (MDS), chronic myeloid leukemia (CML) or other myeloproliferative disorder.
  • Juvenile myelomonocytic leukemia (JMML) in CR, or relapse with less than 10% bone marrow blasts.
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  • CML with tyrosine kinase inhibitor failure in chronic or accelerated phase or evolved to acute leukemia.
  • MDS or other myeloproliferative disorder with life-threatening cytopenia(s), and/or red blood cell or platelet transfusion dependence, or patients with aplasia, or patients with excess blasts less than 10% blasts in the bone marrow at work-up.
  • Aggressive lymphoma: patients in CR1 with disease at high risk of relapse or CR2-3.
  • Indolent lymphoma or chronic lymphocytic leukemia (CLL): any disease status provided any transformed component is in CR.
  • Hodgkin's lymphoma that is primary refractory or relapsed not suitable for other therapy and in PR or CR or small volume stable disease.
  • Performance status:
  • Karnofsky score ≥ 70 or Lansky score ≥ 70.
  • Organ function:
  • Resting left ventricular ejection fraction (LVEF) ≥ 50%.
  • Spirometry (FEV1 and FVC) \& corrected DLCO ≥ 50% predicted. In small children use history and physical and CT scan to determine pulmonary status.
  • Total bilirubin ≤ to 1.5 mg/dl (unless benign congenital elevated bilirubin); ALT ≤ 3 x upper limit of normal (ULN).
  • Calculated creatinine (calc. creat.) clearance ≥ to 60 ml/min.
  • Albumin ≥ 3.0.
  • Graft:
  • o Cryopreserved dose will be ≥ 1.5 x 10^7 TNC/kilogram in each unit for double unit CB grafts. This will be the CB graft for the majority of patients.
  • In select patients with access to CB units that have high TNC (> 5.0 x 10^7/kg), and are from good quality CB banks a single unit could be considered with a back-up CB unit on standby.
  • In select patients who have a very poor search and only have one suitable CB unit available, this unit could be given as a single unit. This unit must have a TNC ≥ 2.0 x 10^7 TNC/kilogram and a CD34+ cell dose ≥ 1.5 x 10^5 CD34+/kilogram.
  • Haploidentical donors who are 5/10 or better but not HLA-identical will be used as outlined in section 6.4.
  • Assignment of conditioning intensity (high dose vs reduced intensity) will be based on patient disease status, age, extent of prior therapy, organ function and presence of significant comorbidities as outlined in Section 9.2.
  • For the purposes of analysis (not assignment of preparative regimen), patients will be assigned to Arms A and B as summarized below according to their risk of early post-transplant death.
  • Eligible patients who fulfill all of the following criteria will be assigned to risk Arm A:
  • Age 2-49 years Diagnosis Any acute leukemia in CR1 - CR2 (includes therapy-related and arising from MDS or myeloproliferative disease). JMML in CR. CML with TKI failure \& < 5% blasts. MDS with < 5% blasts at work-up. Lymphoma (including CLL) CR1-2.
  • Performance Status Karnofsky ≥ 80; Lansky ≥ 80 Organ Function Resting LVEF ≥ to 60% Spirometry (FEV1 and FVC) \& corrected DLCO ≥ 80% predicted. Total bilirubin normal; ALT normal-1.4 x ULN. Calc. creat. clearance ≥ 70 ml/min.
  • Prior HSC Transplant No HCT-CI score^23 0-2 Pre-thaw TNC Dose Each unit ≥ to 2.0 x 10^7/kg
  • Eligible patients who meet any of the following criteria will be assigned to risk Arm B:
  • Age 50-70 years Diagnosis Any acute leukemia in relapse/ refractory disease in BM or circulating blasts or CR3 or aplasia. JMML not in CR. MDS with aplasia or ≥ 5% blasts. Lymphoma (including CLL) with disease other than CR1-2. Severe myelofibrosis of the bone marrow Performance Status Karnofsky 70; Lansky 70 Organ Function LVEF 50-59%. Spirometry \& corrected DLCO 50-79% predicted. Total bilirubin 1.1-1.5 mg/dl; ALT 1.5-3 x ULN. Calc. creat. clearance 60-69 ml/min. Prior HSC Transplant Yes HCT-CI score23 3 or higher Pre-thaw TNC Dose Either or both units 1.5-1.9 x 10^7/kg.

Who cannot join

  • Active CNS leukemia.
  • Any acute leukemia (including prior myelodysplasia or CML blast crisis) with morphologic relapse or persistent disease ≥ 10% blasts in the BM, or doubling of the blasts in the blood in the 2 weeks preceding admission, or need for hydroxyurea in the 2 weeks prior to admission, or uncontrolled extra-medullary disease.
  • Two prior stem cell transplants of any kind.
  • One prior autologous stem cell transplant within the preceding 12 months.
  • One prior allogeneic stem cell transplant within the preceding 24 months.
  • Prior radiation therapy with 400 cGy or more of TBI. If 200 cGy of prior TBI then only 400 CGy of TBI on this protocol is permitted.
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  • Uncontrolled viral, bacteria or fungal infection at time of study enrollment.
  • Sero-positive or NAT positive for HIV.
  • Females who are pregnant or breast feeding.
  • Patient or guardian unable to give informed consent or unable to comply with the treatment protocol including appropriate supportive care, follow-up, and research tests
  • Cord Blood Grafts:
  • Units will be selected based on the HLA-match to the patient and individual cell doses of the units according to current MSKCC unit selection criteria. HLA-testing will be done using molecular techniques. The standard cord blood graft for this protocol will consist of 2 units as a double unit graft although single units are permitted. Each unit will be at least 4 of 6 HLA-A, -B antigen and -DRB1 allele matched with the recipient. Each unit of a double unit graft will have a cryopreserved dose of at least 1.5 x 10^7 TNC/recipient body weight (TNC/kg). In the occasional patient with a large well matched good quality single unit or the rare patient with only one unit of suitable match and dose characteristics the cord blood graft can consist of a single unit as described in section 6.1 .
  • Haploidentical Donor Inclusion Criteria:
  • A HLA-haploidentical related donor will be selected as available as per standard MSKCC Adult BMT guidelines. Mismatched family members who are matched at more than 5 of 10 HLA-loci are permitted. Factors to be taken into account when selecting a haplo-identical donor will include donor age, weight, health status and comorbidities, compliance, venous access, recipent donor specific HLA-antibody status, and NK cell alloreactivity.
  • The donor must meet criteria outlined in the FACT-approved SOP for "DONOR EVALUATION AND SELECTION FOR ALLOGENEIC TRANSPLANTATION" in the Blood and Marrow Transplant Program Manual, document E-1 (see attached, or link to URL:(https://one.mskcc.org/sites/pub/corp/bmt/Documents/D2_SOP_Donor%20Selection%20and%20Evaluation_04_2015.pdf)
  • The donor must have adequate peripheral venous catheter access for leukapheresis or must agree to placement of a central catheter.
  • The donor must be >25 kg in weight.
  • Haploidentical Donor Exclusion Criteria:
  • Evidence of active infection (including active urinary tract infection, or upper respiratory tract infection) or evidence of viral hepatitis exposure on screening unless only HbsAb+ and HBV DNA negative.
  • Medical or physical reason which makes the donor unlikely to tolerate or cooperate with growth factor therapy and leukapheresis.
  • Factors which place the donor at increased risk for complications from leukapheresis or G-CSF therapy (e.g., active autoimmune disease, sickle cell trait, symptomatic coronary artery disease requiring therapy).
  • Pregnancy (positive serum or urine β-HCG) or breastfeeding. Women of childbearing age must avoid becoming pregnant while on the study.

Trial locations and contacts

1 site in 1 country.

United States1 site
  • Memorial Sloan Kettering Cancer Center

    New York, New York, 10065

Other trials in United States

About this study

Official title: Myeloablative Unrelated Donor Cord Blood Transplantation With T-Cell Depleted Haplo-identical Peripheral Blood Stem Cells for Patients With High Risk Hematological Malignancies

The purpose of this study is to find out whether the addition of blood stem cells from a close family member, when added to umbilical cord blood will make the transplant safer.

Read the detailed description

This is a phase 2 study to obtain an estimate of the speed of neutrophil recovery after myeloablative double-unit cord blood (CB) transplantation (CBT) with abrogation of prolonged cytopenia by the infusion of T-cell depleted peripheral blood stem cells (PBSC) from a haplo-identical family member. The CB graft will consist of two units from unrelated newborn donors and haplo-identical related PBSC. Candidates for this trial will include patients aged 2-70 years with high-risk or advanced forms of hematologic malignancies for whom an allogeneic hematopoietic stem cell transplant is indicated and for whom no suitably human leukocyte antigen (HLA)-matched and readily available unrelated donor exists. Patients will receive myeloablative conditioning and cyclosporine-A/ mycophenolate mofetil. CB grafts will consist of two CB units 4-6/6 HLA-matched to the patient to augment graft cell dose and additional T-cell depleted PBSC from a haplo-identical donor. The aim of the haplo-identical PBSC graft is to facilitate transient engraftment and consequent abrogation of the prolonged cytopenia normally associated with CBT by providing a myeloid bridge until CB engraftment occurs.

Being tested
CliniMACS Fractionation system (Arm A), CliniMACS Fractionation system (Arm B), Haploidentical donor CD34+ cells
Keywords
CYCLOPHOSPHAMIDE (CYTOXAN), CYCLOSPORINE, FLUDARABINE, G-CSF, MYCOPHENOLATE MOFETIL (MMF), Cord Blood Transplantation, CliniMACS, 12-153
Medical subject headings
Leukemia, Myelodysplastic Syndromes, Lymphoma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • CliniMACS Fractionation system (Arm A)Device

    7 days before transplant Admit to hospital. Line insertion 6 days before transplant Fludarabine (chemotherapy) Cyclophosphamide (chemotherapy) 5 days before transplant Fludarabine Thiotepa 4 days before transplant Fludarabine Thiotepa 3 days before transplant Fludarabine Start CSA and MMF 2 days before transplant Fludarabine and TBI (radiation therapy)

    1 day before transplant TBI (radiation therapy) Day of transplant Transplant day (infuse cord blood) Day after cord blood transplant Infuse family member stem cells 7 days after transplant Start G-CSF

  • CliniMACS Fractionation system (Arm B)Device

    8 days before transplant Admit to hospital. Line insertion 7 days before transplant Fludarabine 6 days before transplant Fludarabine Cyclophosphamide 5 days before transplant Fludarabine Cyclophosphamide 4 days before transplant Rest 3 days before transplant TBI x 3 Start CSA and MMF 2 days before transplant TBI x 3

    1 day before transplant TBI x 3 Day of transplant TBI x 2 then infuse cord blood

    1 day after the cord blood transplant Infuse family member stem cells 7 days after transplant Start G-CSF

  • Haploidentical donor CD34+ cellsBiological

    CB grafts will consist of two CB units 4-6/6 HLA-matched to the patient to augment graft cell dose and additional T-cell depleted PBSC from a haplo-identical donor.

Study groups in NCT01682226
Study groupRoleWhat they receive
A: standard risk groupExperimentalThis is a 2 arm phase 2 study to obtain an estimate of the speed of neutrophil recovery after myeloablative CBT with abrogation of prolonged cytopenia by infusion of haploidentical family member T-cell depleted PBSC in patients with high-risk or advanced hematologic malignancies.
Receives: Device: CliniMACS Fractionation system (Arm A); Biological: Haploidentical donor CD34+ cells
B: high risk groupExperimentalThis is a 2 arm phase 2 study to obtain an estimate of the speed of neutrophil recovery after myeloablative CBT with abrogation of prolonged cytopenia by infusion of haploidentical family member T-cell depleted PBSC in patients with high-risk or advanced hematologic malignancies.
Receives: Device: CliniMACS Fractionation system (Arm B); Biological: Haploidentical donor CD34+ cells

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Percent of Engrafted Participants With Successful Neutrophil Recovery

    The primary endpoint is neutrophil recovery ie the speed [median (range) days to recovery] and success [day 45 cumulative incidence percent].

    Measured: Day 45

Secondary outcomes (1)
  1. Overall Survival

    78 adult patients were transplanted and received protocol therapy and that patient number was analyzed.

    Survival was analyzed in clinically meaningful patient groups according to having received protocol therapy, the diagnosis and patient comorbidity and have been published separately from the primary endpoint of engraftment.

    Measured: up to 6 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted10 Sep 2012 (estimated)
  2. Study start5 Sep 2012
  3. Primary completion8 Jan 2021
  4. Study completion8 Jan 2021

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
84 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01682226
Sponsor's protocol ID
12-153
Status last verified
Jan 2021
First submitted
6 Sep 2012
Last updated
5 Aug 2022

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing CliniMACS Fractionation system (Arm A), CliniMACS Fractionation system (Arm B) and Haploidentical donor CD34+ cells in people with Leukemia and Myelodysplastic Syndrome, run by Memorial Sloan Kettering Cancer Center at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 32 inclusion and 22 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 5 Aug 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 5 Aug 2022). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Percent of Engrafted Participants With Successful Neutrophil Recovery (time frame: Day 45). It is what the study was designed to measure, not a finding.

Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Aug 2022.

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